Safety of SGI-1776, A PIM Kinase Inhibitor in Refractory Prostate Cancer and Relapsed/Refractory Non Hodgkin's Lymphoma
This study has been terminated.
(The dose limiting toxicity of cardiac QTc prolongation was identifiedin the phase 1 study in patients with refractory prostate and lymphoma)
Information provided by (Responsible Party):
First received: February 19, 2009
Last updated: December 1, 2011
Last verified: December 2011
Patients with hormone and docetaxel refractory prostate cancer or relapsed/refractory non-Hodgkin's lymphoma for which no available standard therapy or therapy which may provide clinical benefit is available will be enrolled. Primary objectives: estimate the maximum tolerated dose and dose-limiting toxicities. Secondary objectives: Response rate, pharmacokinetic and pharmacodynamic profiles, Prostate Specific Antigen response and renal elimination.
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
||Safety Study to Determine the Maximum Tolerated Dose, Pharmacokinetics and Pharmacodynamics of SGI-1776, a PIM Kinase Inhibitor, in Subjects With Hormone and Docetaxel Refractory Prostate Cancer and Relapsed/Refractory Non Hodgkin's Lymphoma
Primary Outcome Measures:
- MTD & DLT [ Time Frame: July 2011 ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Response rate, pharmacokinetics, PSA response, renal elimination and pharmacodynamic effects on biomarker modulation. [ Time Frame: July 2011 ] [ Designated as safety issue: Yes ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||October 2010 (Final data collection date for primary outcome measure)
Starting dose 100 mg (total daily dose) administer as 50 mg every 12 hours for 14 days of a 21-day cycle, dose escalation in successive cohorts until progression or toxicity develops
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Read, understand and sign the IRB- or IEC-approved ICF confirming his or her willingness to participate in this trial.
- At least 18 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Adequate bone marrow function; normal renal and hepatic function, normal cardiac function.
- Normal cardiac function in the opinion of the investigator and supported by LVEF 50% or greater on the screening echocardiogram (or MUGA), no significant abnormalities on the screening ECG (eg, left bundle branch block, III degree AV block, acute myocardial infarction, Wolff-Parkinson-White syndrome or QTc interval ≥ 450 msec) and no history of additional risk factors for torsades de pointes (eg, heart failure, hypokalemia or family history of Long QT Syndrome).
- Active secondary malignancy or history of other malignancy within the last two years except non-melanoma skin cancers or cervical carcinoma in situ.
- History of significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure and/or myocardial infarction or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
- Received any anticancer agent(s) within the past 3 weeks, including investigational agents, chemotherapy (6 weeks for nitrosoureas or mitomycin), immunotherapy, biologic or marketed or investigational tyrosine kinase inhibitors.
- Received prior radiation therapy within the past 4 weeks or received irradiation of ≥ 25% of their bone marrow reserve.
- Any serious, uncontrolled active infection that requires systemic treatment or known infection with HIV, HCV or HBV.
- Symptomatic CNS metastases or lesions for which treatment is required.
- Males with histologically confirmed adenocarcinoma of the prostate, which is now metastatic (e.g., any T, any N, M1a-c)based on bone scan, CT scan, or MRI scan. Demonstrated evidence of progressive disease despite androgen deprivation (androgen ablation or surgical castration), anti-androgen withdrawal and progression of disease after docetaxel-based therapy.
Demonstrated evidence of progressive disease despite androgen deprivation (androgen ablation or surgical castration), anti-androgen withdrawal and progression of disease after docetaxel-based therapy.
• Greater than 25% increase in 3 consecutive tests (PSA 1 < PSA 2 < PSA 3), each PSA value separated by at least 1 week
- Serum testosterone level ≤ 50 ng/dL post orchiectomy or while maintained on continuous or intermittent medical androgen suppression with a LHRH agonist or antagonist.
- At least 4 weeks since prior flutamide, megestrol, ketoconazole, aminoglutethimide; and at least 6 weeks since prior bicalutamide or nilutamide.
- Systemic corticosteroids discontinued within two weeks of dosing, except low dose regimens which may continue if unchanged
- Strontium-89 or Samarium-153 must have been completed at least 8 weeks prior to the first dose of therapy and recovered from all treatment-related toxicities.
1. Must not be receiving concurrent anti-androgen hormonal therapy for hormone refractory prostate cancer.
- Histologically proven relapsed or refractory non-Hodgkin's lymphoma subjects for which there is no available standard therapy or therapy which may provide clinical benefit.
- Measurable disease (at least 1 lesion ≥ 1.5 cm).
- Bulky disease by CT, defined as any single mass >10 cm in its greatest diameter.
- Systemic corticosteroids within 2 weeks, except low dose regimens which may continue if unchanged.
- Received any radiopharmaceutical therapy within the past six weeks.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00848601
|Los Angeles, California, United States, 90095-1678 |
|Cancer Therapy Research Center
|San Antonio, Texas, United States, 78229 |
|Royal Marsden Hospital
|Sutton, England, United Kingdom, SM2 5PT |
No publications provided
History of Changes
|Other Study ID Numbers:
|Study First Received:
||February 19, 2009
||December 1, 2011
||United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Keywords provided by Astex Pharmaceuticals:
Hormone & Docetaxel refractory Prostate Cancer
Refractory non-Hodgkin's Lymphoma
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on September 30, 2014
Genital Neoplasms, Male
Neoplasms by Site
Genital Diseases, Male
Neoplasms by Histologic Type
Immune System Diseases